Improving benefit-harm assessment of glucocorticoid therapy incorporating the patient perspective: The OMERACT glucocorticoid core domain set.

OBJECTIVE: Our primary objective was to develop an Outcome Measures in Rheumatology (OMERACT) core domain set to capture the impact of glucocorticoids (GC), both positive and negative, on patients with Rheumatic conditions. METHODS: The OMERACT Filter 2.1 was used to guide core domain selection. Systematic literature reviews, qualitative studies and quantitative surveys were conducted by the OMERACT GC Impact working group to identify candidate domains for a core domain set. A summary of prior work and Delphi exercise were presented at the OMERACT 2020 virtual GC workshop. A proposed GC Impact core domain set derived from this work was presented for discussion in facilitated breakout groups. Participants voted on the proposed GC Impact core domain set. RESULTS: 113 people, including 23 patient research partners, participated in two virtual workshops conducted at different times on the same day. The proposed mandatory domains to be evaluated in clinical trials involving GCs were: infection, bone fragility, hypertension, diabetes, weight, fatigue, mood disturbance and death. In addition, collection of disease specific outcomes was included in the core domain set as "mandatory in specific circumstances". The proposed core domain set was endorsed by 100% (23/23) of the patient research partners and 92% (83/90) of the remaining participants, including clinicians, researchers and industry stakeholders. CONCLUSION: A GC Impact core domain set was endorsed at the OMERACT 2020 virtual workshop. The OMERACT GC Impact working group will now progress to identify, develop and validate measurement tools to best address these domains in clinical trials.

Improving Benefit-harm Assessment of Therapies from the Patient Perspective: OMERACT Premeeting Toward Consensus on Core Sets for Randomized Controlled Trials.

OBJECTIVE: Outcome Measures in Rheumatology (OMERACT) convened a premeeting in 2018 to bring together patients, regulators, researchers, clinicians, and consumers to build upon previous OMERACT drug safety work, with patients fully engaged throughout all phases. METHODS: Day 1 included a brief introduction to the history of OMERACT and methodology, and an overview of current efforts within and outside OMERACT to identify patient-reported medication safety concerns. On Day 2, two working groups presented results; after each, breakout groups were assembled to discuss findings. RESULTS: Five themes pertaining to drug safety measurement emerged. CONCLUSION: Current approaches have failed to include data from the patient's perspective. A better understanding of how individuals with rheumatic diseases view potential benefits and harms of therapies is essential.

A Survey of Glucocorticoid Adverse Effects and Benefits in Rheumatic Diseases: The Patient Perspective.

OBJECTIVE: The aim of this study was to explore, from the patient's perspective, the beneficial and adverse effects (AEs) of glucocorticoids (GCs) in patients with rheumatic diseases, to be used in the development of a patient-reported outcome measure. METHODS: A cross-sectional survey, capturing benefits and AEs of GC use, was administered to 2 groups of patients: (1) those attending a tertiary rheumatology clinic with various rheumatic diseases who had used GCs within the past year and (2) patients from the Hospital for Special Surgery rheumatoid arthritis database. RESULTS: Cohort 1 had 55 GC users, and cohort 2 had 95 GC users and 29 nonusers. The majority of GC users in both cohorts reported at least 1 AE (100%, 86%). The AE prevalence per person was 50% higher in cohort 1 compared with GC users in cohort 2 (7.7 vs. 5.3; AE ratio, 1.5; 95% confidence interval, 1.3-1.7) and 2-fold greater in cohort 2 GC users compared with GC nonusers (5.3 vs. 2.6; AE ratio, 2.0; 95% confidence interval, 1.6-2.6). In both cohorts, AEs identified as "worst" by GC users included skin thinning/easy bruising, sleep disturbance, mood disturbance, and change in facial shape. Most felt GCs helped their disease "a lot" (78%/62%) and that the benefits were greater than the AEs (55%/64%). Many AEs were more frequent in GC users than in nonusers. CONCLUSIONS: Patients receiving GC therapy for rheumatic conditions report a large number of AEs and those that have the greatest life impact are often difficult for physicians to measure. These results will inform the development of a patient-reported outcome measure to capture the effects of GCs from the patient's perspective.

Relationship between area-level socio-economic deprivation and autoantibody status in patients with rheumatoid arthritis: multicentre cross-sectional study.

OBJECTIVES: The aims of this study were to assess the association between area-level socio-economic deprivation and the phenotype of rheumatoid arthritis (RA), defined by rheumatoid factor (RF) and anticitrullinated peptide antibody (AC PA) status, and to determine whether any observed association can be explained by smoking. METHODS: The authors performed logistic regression analysis of 6298 patients with RA, defined by American College of Rheumatology classification criteria modified for genetic studies. Analysis was stratified by cohort/recruitment centre. Socio-economic deprivation was measured using the Townsend Index. RESULTS: Deprivation predicted RF but not ACPA positivity, independent of smoking. The ORs for trend across tertiles, adjusted for smoking, gender, period of birth and cohort/recruitment centre, were 1.14 (95% CI 1.01 to 1.29) for RF and 1.01 (95% CI 0.87 to 1.16) for ACPA. Even after adjusting for deprivation, smoking was strongly associated with ACPA positivity (OR 1.38, 95% CI 1.22 to 1.55). There was no evidence of any effect modification by the RA risk alleles (HLA-DRB1 shared epitope and PTPN22 rs2476601) that have previously been shown to modify the effect of smoking on ACPA and RF positivity. CONCLUSIONS: Among patients with RA, deprivation predicted RF positivity but not ACPA positivity. The effect of deprivation did not appear to be explained by smoking. Deprivation may be a marker for previously unrecognised, potentially modifiable environmental influences on the immunological phenotype of RA. Furthermore, given the known associations of RF positivity with prognosis and response to treatment in RA, these findings have potential implications for resource allocation and healthcare delivery.

Ischaemic manifestations in giant cell arteritis are associated with area level socio-economic deprivation, but not cardiovascular risk factors.

OBJECTIVES: To determine whether ischaemic manifestations of GCA are associated with pre-existing hypertension, atherosclerosis or area-level socio-economic deprivation. METHODS: We conducted an observational study of rheumatologist/ophthalmologist-diagnosed GCA in eight UK centres. The main outcome measure was ischaemic manifestations observed during active GCA: visual loss/blurring, aura, diplopia, jaw/tongue/limb claudication, cerebral/myocardial ischaemia or scalp necrosis. RESULTS: Out of 271 patients, 222 had ischaemic manifestations. Adjusted odds ratios (ORs) for the influence of hypertension and atherosclerosis were 1.6 (95% CI 0.8, 3.1) and 1.5 (0.6, 3.5). The most striking finding was an association of ischaemic manifestations with increasing Index of Deprivation 2007 score: OR 4.2 (95% CI 1.3, 13.6) for the most-deprived quartile compared with the least-deprived quartile. Similar effect sizes were seen within each recruitment centre. Deprivation was associated with smoking and negatively associated with previous polymyalgia. However, neither of these variables, nor hypertension or atherosclerosis, appeared responsible for mediating the effect of deprivation on ischaemic complications. Smoking was not associated with ischaemic manifestations. Median symptom duration before treatment was 30 days; after adjusting for symptom duration, the OR for ischaemic complications was 3.2 (95% CI 1.0, 10.8) for the most-deprived quartile compared with the least-deprived quartile. CONCLUSIONS: In GCA, area-level socio-economic deprivation was associated with ischaemic manifestations: this was not mediated by traditional cardiovascular risk factors. These findings are novel and require replication. Delay between first symptoms and treatment may play a role. Public awareness campaigns about GCA should aim especially to engage individuals living in more deprived areas to encourage early presentation and prompt treatment.